Biocidal polyurethane systems, methods of making and use thereof

Abstract

The present invention relates to the field of polymers, in particular to polyurethane (PU) based polymer systems with broad spectrum biocidal activity and their use for the manufacture of biocidal products. The present invention provides a method for providing a biocidal polyurethane-iodine (PU-I) complex comprising (i) dissolving at least one iodine source into one or more raw materials used for the preparation of the desired polyurethane (PU) to obtain a single phase iodine system, followed by (ii) conducting the PU polymerization reaction in the presence of the single phase iodine system, thereby generating the biocidal PU-I complex in situ.

Description

[0001] The present invention relates to the field of polymers, and more specifically, to polymeric systems based on polyurethanes (PU) with broad spectrum biocidal activity and their use in the manufacture of biocidal articles. More specifically, it relates to polyurethane-iodine (PU-I) complexes, including methods of their manufacture, their mechanical and biocidal properties, and various applications of the PU-I materials.

[0002] Polyurethanes (PU) are used in a wide variety of markets and applications. The materials can be thermoset or thermoplastic, rigid and hard or flexible and soft. The materials can be readily extruded and molded into almost an infinite number of shapes and forms, including coatings, filaments, sheets, molded parts, fibers, and foams. The materials have good hardness, tensile strength, compressive strength, impact resistance, abrasion resistance, and tear strength. The range of applications for PU is broad, including: filters, foams, insulation, wound coverings, catheters, foam seating, mattress, rigid foam insulation board, seals and gaskets, durable elastomeric wheels, bushings, electrical coverings, panels, adhesives, surface coatings and sealants, synthetic fibers, carpet underlay, hard plastic parts, condoms, hoses, air and liquid filters, flexible tubing, medical devices, and food packaging, among others. The PU materials can be further compounded with many other natural and synthetic rubbers and polymers to create compounds and interpenetrating polymer networks for related and other applications.

[0003] Traditionally, urethane groups are formed by the reaction of an alcohol with an isocyanate. PUs are generally made by the reaction of a polyol with an isocyanate. The reaction is illustrated as follows.

[0004]

[0005] Thus, urethane groups are formed by the reaction of an alcohol with an isocyanate. When an alcohol with functionality > 2 is reacted with an isocyanate with functionality > 2 to form an alternating copolymer, a polyurethane is formed. To better define and distinguish the types of alcohols used in polyurethane reactions, the following terms are commonly used: polyol, chain extender, and crosslinker.

[0006] Polyols generally refer to polymeric, capped hydroxyl compounds with a large molecular weight and functionality > 2, while chain extenders are low molecular weight, capped hydroxyl and amine compounds with functionality = 2, and crosslinkers are low molecular weight, capped hydroxyl and amine compounds with functionality > 3. The following table gives examples of the types of "alcohols" used in polyurethane reactions.

[0007]

[0008] While the actual combination of hydroxyl group-containing compounds that can be mixed and reacted to form a polyurethane is almost infinite, the formation of the polyurethane linkage is the same for all compounds: the reaction of an alcohol hydroxyl group with an isocyanate.

[0009] Acceptable isocyanates also come in a range of functionalities, including diisocyanates (functionality = 2), triisocyanates (functionality = 3) and polyisocyanates (functionality > 3). They are available as aliphatic or aromatic isocyanates.

[0010] Thermoplastic polyurethanes (TPU) and thermoset polyurethanes can be distinguished. Thermoplastic polyurethanes are materials in which physical crosslinks are formed between the phases in the polyurethane, which can be "melted" upon the application of heat or solvent. These polymers can be extruded by injection molding and by hot melt extrusion. The material can also be dissolved in a solvent. The reason that the material can be "melted" is that it is not chemically crosslinked, since the polymerization reaction is usually between a diol and a diisocyanate, both of which have a functionality of 2. As a result, a linear polyurethane is formed. Thermoplastic polyurethanes are polymers that can be melted and reformed, and have elasticity and high flexibility, making them versatile materials suitable for a wide range of industries.

[0011] Thermoset polyurethanes are chemically crosslinked, and the resulting material cannot be "melted" and reformed. Thermoset PUs are usually more durable than thermoplastic polyurethanes. The reason for this is that the alcohol and / or isocyanate system used has a functionality greater than 2. The use of higher functionality raw materials (functionality > 2) increases the possibility of chemically linking polymer chains until an infinite crosslinked structure is obtained, which cannot be degraded by heating or dissolution.

[0012] In general, polyurethane foams are desired, and polyurethane foams require the addition of a blowing agent and a surfactant. The blowing agent can be a volatile liquid, such as a low-boiling hydrocarbon or a hydrofluorocarbon, or more preferably an inert gas. Carbon dioxide is a particularly preferred blowing agent, which can be added directly as a gas or produced by adding water to the polyurethane reaction. The water reacts quickly with the isocyanate to produce an amine and carbon dioxide. The amine thus produced further reacts with more isocyanate to produce a urea linkage in the polymer, and the carbon dioxide thus produced acts as a blowing agent to produce a polyurethane foam. A schematic of this process is as follows.

[0013]

[0014] Thus, the addition of water to the polyurethane reaction produces both polyurethane and urea linkages in the final foam matrix.

[0015] Although PUs have excellent mechanical properties, the material does not have biocidal properties, and microorganisms readily proliferate on the surface of PUs. PUs are susceptible to attack by microorganisms, which is considered to be one of the major drawbacks of this large class of polymers.

[0016] Bacterial growth on industrial and household PUs is annoying and undesirable, while bacterial growth on PUs for medical applications can be fatal. The article “Antimicrobial strategies to reduce polymer biomaterial infections and their economic implications and considerations”, International Biodeterioration & Biodegradation, 136 (2019) 1-14, describes the problem of hospital acquired infections (HAIs), how medical devices contribute to the occurrence of HAIs, and various strategies for rendering polymers in medical devices antimicrobial. Catheters are the most common implants worldwide, with 5 million central venous catheters (CVCs) and 300 million urinary catheters being implanted in the United States each year. Both types of catheters are considered to be two of the main sources of HAIs. The U.S. Centers for Disease Control and Prevention (CDC) reports that approximately 250,000 CVC-associated bloodstream infections (BSIs) occur each year in the United States, with an additional hospitalization cost of approximately $34,500-56,000 per infection. This has not only huge economic costs, but according to the CDC, 4% of patients in the United States will contract an HAI during a hospital stay, which will result in 1.7 million infections and 99,000 related deaths.

[0017] The article also points out that relatively few microorganisms are responsible for most HAIs, mainly Staphylococcus aureus, Pseudomonas aeruginosa, Escherichia coli, coagulase-negative staphylococci (CoNS), mainly Staphylococcus epidermidis, and Enterococcus, mainly Enterococcus faecalis and Enterococcus faecium. Vascular implants are more likely to be colonized by S. aureus and CoNA, while E. coli and Enterococcus are more likely to colonize urinary system devices.

[0018] PU is commonly used in many medical applications, including vascular and urinary catheters, wound dressings, tubing, medical device packaging, filters, hospital bed linens, surgical drapes, feeding tubes, surgical drains, intra-aortic balloon pumps, dialysis equipment, non-allergenic gloves, medical garments, and various injection molded devices. The most common use of PU is short-term implants, where the potential for microbial contamination is high. It would be a great benefit if these medical devices and health-related products could be made biocidal to reduce the spread of undesirable pathogenic microorganisms leading to HAI. HAI is caused by the spread of viral, bacterial, and fungal pathogens from healthcare visits or care, such as hospitals, doctors' offices, nursing homes, etc. The most common ways of acquiring HAI are through bloodstream infections, pneumonia, urinary tract infections, and surgical site infections. PUs are responsible for manufacturing a variety of products that come into direct contact with wounds, airways, blood, and urinary tracts, and thus are a potential source of pathogenic contamination risk leading to HAI. If not the source, PUs can be a place where undesirable microbial buildup is facilitated, leading to undesirable infections.

[0019] In view of the foregoing, it would be highly desirable to have a PU or PU-based material with biocidal activity for certain applications, particularly those that can improve the health of consumers and patients and reduce the risk of HAI.

[0020] There are a number of patents and literature describing the biocidal properties of polyurethane materials by incorporating antimicrobial agents into the PU polymerization. These agents can be either a reactant that is fixed into the PU structure and / or an additive that is contained in the PU matrix. The biocides include: quaternary amino compounds (such as benzalkonium chloride and cetylpyridinium chloride); phenol and cresol; halogenated phenols (such as p-chloro-m-cresol); biguanides (such as chlorhexidine); anilines (such as triclosan); and triclosan.

[0021] One class of antimicrobial agents that has received great attention and is responsible for many commercial systems is the use of metals, such as copper, zinc, silver, and their respective derivatives and / or salts. These metal systems are coated onto or blended into polymeric substrates. Nano-silver, in particular, is chosen as a desirable antimicrobial metal that can impart biocidal properties to coated or extruded systems. While these systems are promising and have achieved some commercial success, there are problems with the use of metal and nano-metal systems. First, the metals can leach and / or be removed from the PU system. One study on laundering of nano-silver impregnated fabrics showed that the level of nano-silver removed from the garments was 20-35% after only one wash. Second, the toxicity of metal, and in particular, nano-metal systems is not fully understood. Nano-metal systems have the ability to penetrate skin / cell barriers, and therefore, there are concerns about patient safety. Nano-metal systems can also leach or be removed from treated systems and enter the ecosystem, and the environmental impact of these metal nanoparticles is not known.

[0022] With respect to antimicrobial agents, there are also many references to making PUs antimicrobial by adding known antibiotic agents to the PU system. Unfortunately, the widespread use of antibiotics has led to the development of some bacteria that are resistant to antibiotics or are known as "superbugs." This development is particularly troublesome because the potential for acquiring untreatable HAIs increases dramatically, which has a direct impact on patient health.

[0023] Based on the foregoing, it is clear that the discovery of new biocidal PU materials that can combat existing and future antimicrobial superbugs and viruses and the use of products incorporating said biocidal materials would be highly desirable.

[0024] One unique attribute of polyurethanes is that polyurethane linkages form strong complexes with iodine. Iodine is a unique material because it is a naturally occurring, environmentally benign material that is readily available, inexpensive, and exhibits strong killing activity against bacteria, viruses, and fungi, while also being an essential mineral nutrient required for normal healthy function of the human body. The actual complexation mechanism is believed to be similar to that of the water soluble polyvinylpyrrolidone-iodine (PVP-I) iodophor complex. PVP-I (betadine) is commercially available and is widely used as a disinfectant for skin disinfection prior to and after surgery and for minor wounds. The actual PVP-I complexation is described as occurring in the following manner.

[0025]

[0026] It is generally believed that this complexation occurs through hydrogen bond / charge complexation between the amide functionality on the PVP and the iodine to form a donor-acceptor complex, with iodine being the acceptor. Similar donor-acceptor complexation is envisioned to occur with the carbamate and urea groups in polyurethanes.

[0027]

[0028] PVP-I is a water soluble iodophor which is widely used as a disinfectant in the healthcare and veterinary fields. PVP-I was introduced in the 1950s and is a complex of polyvinylpyrrolidone (PVP) with iodine (I). The PVP-I material is a stable complex which has a broad spectrum of antimicrobial activity similar to iodine but with less irritation and toxicity. PVP-I containing formulations do not require the poison label required for iodine products and commercial solutions and ointment based formulations are readily available over the counter (OTC products). PVP-I solutions are non-irritating, non-sensitizing and do not cause pain when applied to wounds or mucous membranes. PVP-I solutions can be used as a mouthwash without staining or adverse side effects. PVP-I solutions are effective against: bacteria, bacterial spores, yeasts, molds, fungi, viruses and bacteriophages. The broad spectrum biocidal activity is particularly effective in treating mixed infections. A review of PVP-I can be found in the PVP-I handbook published by International Speciality Products, Inc. handbook Phar00193 / 2004. It is envisaged that a flexible, simple and cost effective production method of polyurethane-iodine complexes which produce polyurethanes with biocidal properties similar to water soluble PVP-I and which are safe, non-irritating, biocidal and antiviral would be of great interest.

[0029] US 3,235,446 discloses how to make iodinated polyurethane foams and films. The initial polyurethane foam is soaked in a water-alcohol iodine solution and the iodine slowly diffuses into the foam. Some disadvantages hinder the commercial viability of this method: (1) the process time is long for the foam to absorb the iodine solution, (2) the foam needs to be dried afterwards, (3) the heterogeneous absorption of iodine throughout the foam, (4) the PU chemical structure of the foam has a large influence on the ability to "absorb" the iodine solution.

[0030] US 4,381,380 discloses how to make iodine treated thermoplastic polyurethane articles. The inventor here uses a pre-made PU thermoplastic article and treats it with a water-alcohol iodine solution.

[0031] US 4,769,013 discloses a germicidal coating for PUs which is produced by: initially treating the PU with an organic solvent solution containing PVP, which causes the PVP polymer to adhere to the PU article, and subsequently treating with an iodine solution which forms the adhered PVP-I germicidal coating.

[0032] US 5,302,392 discloses a PU foam which can release iodine rapidly. The foam is produced by including PVP-I as a solid powder in the PU polymerization process, forming an interpenetrating network (IPN) of solid PVP-I particles dispersed in (i.e. not complexed with) the PU foam matrix. The patent discloses that the resulting foam contains solid particles of PVP-I which are essentially not complexed with the PU matrix. Addition of an aqueous solution to the resulting PU-PVP-I IPN causes the PVP-I complex to be released instantaneously into the liquid. The focus of US 5,302,392 is not to make a PU foam material which is biocidal, but to use the PU foam as a delivery device to deliver water-soluble PVP-I complex upon wetting. There is no reaction to make a PU-I complex and the water-soluble PVP-I is leached from the PU matrix to give instant activity, rather than to provide a PU material which has a long-lasting and controlled biocidal activity.

[0033] While all these prior art methods produce biocidal PU products, to date there have been a number of problems and limitations which have prevented their large-scale application.

[0034] Firstly, all known manufacturing methods require the use of solvents to form the iodine complex. The PU needs to be contacted, soaked in an organic solvent system and then dried. These processes are time consuming, expensive, energy intensive and environmentally unfriendly. Therefore, it is not economically or practically viable to implement these techniques on a large scale. Secondly, the methods are generally only suitable for hydrophilic PUs which interact with and swell in the alcohol-water iodine solution to produce the complex. Hydrophobic PUs which have little or no interaction with polar solvent systems are not expected to work. Thirdly, these methods are difficult to standardize to develop a commercial process where the same iodine-complexed material needs to be produced continuously. Even very small changes in the chemistry and physical structure of the polyurethane can have a potentially large impact on the iodine uptake and complexation process. Finally, as all prior art methods rely on the uptake of iodine from a solution onto the PU substrate - which is a surface application, it is difficult to standardize the level of PU-I, the efficiency of complexation and the depth of complexation. It is almost guaranteed that significant biocidal variations and activity will be observed in the resulting PU-I system, which is not acceptable for a regulated (medical) product.

[0035] In view of the above, the present inventors have set out to provide a new method of manufacturing a PU-I system which overcomes at least some, and preferably all, of the above-mentioned prior art disadvantages. In particular, it aims to provide a simple, stable, homogeneous and intrinsic biocidal PU-I complex which is manufactured without the need for undesirable solvents and / or complex manufacturing processes.

[0036] Surprisingly, the present inventors have found that polyurethanes can be complexed with a suitable iodine source, in the process, the iodine source is directly dissolved in one or more of the raw materials used to make the desired polyurethane, thus forming a polyurethane-I complex "in situ" during the polyurethane polymerization reaction, or the iodine source is added to a "melt" of a preformed polyurethane, where the polyurethane is soluble and can complex the iodine source with the urethane and urea groups in the polyurethane matrix. The preformed PU can be a PU in a thermoplastic PU (TPU) or in an aqueous dispersion (PUD). The iodine source is added, for example, by hot melt extrusion with a TPU, or by migrating the iodine into the dispersed PU phase of a polyurethane dispersion (PUD) in an aqueous continuous phase. Depending on the amount and / or source of iodine used in the process, the biocidal properties of the final PU-I material can be easily adjusted.

[0037] In situ formation of PU-I complex

[0038] One aspect of the present invention relates to a process for providing a biocidal polyurethane-iodine (PU-I) complex, comprising (i) dissolving at least one iodine source into one or more of the raw materials used to make the desired polyurethane (PU), to obtain a single phase iodine system, followed by (ii) conducting the PU polymerization reaction in the presence of the single phase iodine system, thereby producing the biocidal PU-I complex.

[0039] Without wishing to be bound by theory, in this process, the "in situ" formation of the PU-I complex occurs almost simultaneously with the formation of the urethane groups, to form a stable PU-I complex.

[0040] Such a process has not been disclosed or suggested in the art.

[0041] As mentioned above, US 5,302,392 discloses a process for the preparation of a PVP-I / PU foam, wherein a polyethylene glycol slurry of dry PVP-I powder is added to the isocyanate reactants, thus initiating the PU foaming process. Unlike the present invention, the PVP-I is added to the PU reaction mixture in the form of a binary iodine system. Thus, the solid PVP-I complex particles of the polyurethane composition of US 5,302,392 are uniformly distributed throughout the polyurethane matrix, and thus the complex is not bound to the polyurethane to any significant extent. The composition is particularly useful for scouring sponges, which can provide almost instantaneous release of the complex.

[0042] As used herein, the term "raw material" refers to any precursor, reactant or starting material conventionally used to make a polyurethane.

[0043] A "single phase iodine system" or "one phase iodine system" refers to a homogeneous solution of at least one iodine source in any type or amount of polyurethane reaction starting material. This is a homogeneous single phase liquid mixture composed of two or more components, at least one of which is an iodine source (solute) and at least one of which is a component for the subsequent PU reaction (solvent) in which the iodine source is soluble. It does not include mixtures of solid or particulate portions suspended in a liquid, such as slurries or suspensions. For example, it does not include a polyol slurry of dry powder PVP-I.

[0044] It is important to understand that the actual polyurethane reaction and the formation of the carbamate group complexed with iodine are the same for both polyurethane thermoplastic and thermoset materials. The driving force to obtain thermoplastic or thermoset is based on the functionality of the starting materials used in the polyurethane reaction, not a chemical difference (i.e. the same polyurethane reaction of alcohol with isocyanate occurs in both systems). Thus, the ability to form a PU-I complex in situ during the polyurethane reaction applies to both thermoplastic and thermoset polyurethanes.

[0045] According to the present application, the at least one iodine source can be selected from the group consisting of elemental iodine, polyvinylpyrrolidone-iodine (PVP-I), iodide salts, and any combination thereof. The PVP-I can contain 1-25% available iodine and 2-35% total iodine. Preferably, the at least one iodine source is elemental iodine, optionally in combination with PVP-I. In a particular embodiment, elemental iodine is the only iodine source.

[0046] As noted above, the in situ method of the present application is characterized by the at least one iodine source being contained in the PU reaction mixture in a dissolved state, particularly dissolved in one or more starting materials, such as precursors, reactants, solvents, that are typically used to make polyurethanes, whether thermoset or thermoplastic polyurethanes. Suitable starting materials in which the iodine source is dissolved include: (i) polyols; (ii) isocyanates; and (iii) chain extenders, crosslinkers, catalysts, surfactants, solvents, and / or additives used to synthesize polyurethanes.

[0047] Thus, the present application is directed to a method of providing a biocidal polyurethane-iodine (PU-I) complex, the method comprising dissolving at least one iodine source into a polymeric mixture comprising starting materials for making a polyurethane thermoset or a polyurethane thermoplastic; and allowing the biocidal PU-I complex to form. For example, the method suitably comprises dissolving at least one iodine source into a polymeric mixture comprising (i) polyols and (ii) isocyanates and / or small molecule chain extenders, typically used to make polyurethanes, thereby providing a thermoset or thermoplastic polyurethane-iodine complex. Preferably, synthetic or bio-based starting materials are used to produce the polyurethane.

[0048] In one embodiment, the at least one iodine source is first dissolved in an "incomplete" reaction mixture, such that the reaction mixture is completed to initiate the PU reaction. For example, a method is provided wherein the at least one iodine source (e.g., PVP-I and / or I2) is dissolved in a polyol, polyol blend, low molecular weight alcohol having a functionality > 2, low molecular weight amine having a functionality > 2, and / or solvent, and then the desired isocyanate is added to initiate the polyurethane reaction.

[0049] In another embodiment, the at least one iodine source is dissolved in a "complete" PU reaction mixture. For example, the at least one iodine source is dissolved in a polymeric mixture comprising (i) a polyol; (ii) an isocyanate; and (iii) a chain extender, crosslinker, catalyst, surfactant, solvent, and / or additive used in the synthesis of a polyurethane, to provide a thermoplastic or thermoset polyurethane-iodine complex.

[0050] Suitable isocyanates for use in the present application are known in the art. The isocyanate can comprise an aliphatic di-, tri-, or polyisocyanate, an aromatic di-, tri-, or polyisocyanate, or any combination thereof. In one particular aspect, the isocyanate comprises a diisocyanate or a polyfunctional isocyanate that is aliphatic or aromatic.

[0051] Suitable polyols for use in the present application are known in the art. For example, the polyol is selected from the group consisting of a polyether polyol, a polyester polyol, a polycarbonate polyol, a polycaprolactone polyol, a polyacrylate polyol, and any combination thereof.

[0052] The chain extender can be a low molecular weight diol or diamine, or any combination thereof.

[0053] The crosslinker can be a low molecular weight alcohol or amine having a functionality greater than 2.

[0054] The polyurethane catalyst can be any conventional or yet to be discovered PU catalyst, such as a tertiary amine, a metal compound, or any combination thereof. It has been observed that in the presence of a single phase iodine system, the PU polymerization reaction is inhibited by the iodine species. Therefore, in one preferred embodiment, more catalyst is added in order to carry out the polyurethane reaction and the formation of the PU-I complex.

[0055] According to the present application, the in situ formation of the PU-I complex can involve the polyurethane polymerization reaction by multi-step, one-step bulk or solvent polymerization, such that the final PU-I complex is formed in the prepolymer formation stage or one process step.

[0056] Formation of PU-I complex with preformed PU

[0057] The present invention also relates to a method wherein the PU is ensured to complex with the iodine source by using specific conditions, such that the iodine source is complexed with the preformed PU. A method is provided to provide a biocidal polyurethane-iodine (PU-I) complex, the method comprising preparing a homogeneous mixture of (i) at least one iodine source and (ii) a thermoplastic polyurethane (TPU) or a PU dispersion (PUD) to form a single phase system that can form a biocidal PU-I complex.

[0058] Thus, similar to the description of the in-situ method above, the single phase system ensures that the PU structure present is in a "molten" physical state that can interact (complex) with the iodine source.

[0059] The TPU can be brought into a molten physical state in various ways. For example, the TPU can be heated above its glass and / or crystallization temperature, or it can be dissolved in a suitable solvent. Thus, the method comprises preparing a homogeneous single phase system by admixing at least one iodine source with the TPU in a heated, molten or dissolved state. The method can comprise dissolving at least one iodine source in a melt or solution of thermoplastic polyurethane to provide a thermoplastic polyurethane-iodine (TPU-I) complex. Also included is a method of using the TPU-I complex as a masterbatch, further processed into a specific product.

[0060] In one embodiment, it comprises mixing the iodine source and the TPU as a dry powder and feeding the mixture into an extruder. In a specific aspect, the elemental iodine and / or PVP-I is dry mixed with the TPU and then extruded.

[0061] The approach can be practiced with any type of TPU. For example, the thermoplastic polyurethane comprises one or more of a polyester-based, a polyether-based, a polycaprolactone-based, a polyacrylate-based, an aromatic and / or an aliphatic thermoplastic polyurethane. Preferred are polyurethanes produced from synthetic or bio-based starting materials.

[0062] Advantageously, the TPU is the predominant or the major polymer in the homogeneous mixture of (i) at least one iodine source and (ii) a thermoplastic polyurethane (TPU). In one aspect, the TPU comprises at least 85 w%, preferably at least 90 w%, more preferably at least 95 w% or even at least 98 w% of the total polymer content of the homogeneous mixture.

[0063] Preferably, the homogeneous mixture does not contain any hydrophilic polymers, such as poly(N-vinyl lactam).

[0064] Similar to the description of the in-situ method above, the at least one iodine source is selected from the group consisting of elemental iodine, polyvinylpyrrolidone-iodine (PVP-I), iodide salts, and combinations thereof.

[0065] In one embodiment, at least PVP-I is used as the source of iodine. In a preferred embodiment, the PVP-I contains 1-25% available iodine and 2-35% total iodine. Preferably, PVP-I of polyvinylpyrrolidone iodine meeting USP or EP Pharmacopeia is used. In another embodiment, a combination of PVP-I and elemental iodine is used, for example during hot melt extrusion to make the PU-I complex. In a preferred aspect, the at least one source of iodine is or comprises elemental iodine.

[0066] As described below, the present invention provides a method for manufacturing a biocidal polyurethane-iodine (PU-I) complex, for example for use as a biocidal coating, wherein the preparation of a homogeneous iodine / PU mixture comprises adding elemental iodine to an aqueous polyurethane dispersion (PUD) and allowing the elemental iodine to migrate into the PU phase of the dispersion to obtain a homogeneous single phase system in which the PU-I complex is formed.

[0067] Aqueous polyurethane dispersions are known in the art and are readily available from suppliers. For example, aliphatic polyether polyurethane dispersions are available from Rudolf GmbH, Geretsried, Germany.

[0068] In one embodiment, the elemental iodine is added to the PUD in the form of a solution in a suitable solvent that dissolves the elemental iodine and is compatible with the PU phase, for example an alcohol, preferably isopropyl alcohol. See also Example 2 and Figure 1 A. In another embodiment, the elemental iodine is added as a solid material and sublimation of the iodine is then carried out. Iodine readily sublimes at room temperature but can also be catalysed by heating. See Example 2 and Figure 1 B. In another embodiment, the elemental iodine is dissolved in excess alcohol solvent and added to the aqueous PUD to form a single phase aqueous-alcoholic solution and thereby form the biocidal PU-I complex. See Example 2 and Figure 1 C.

[0069] Biocidal PU-I complex and its use

[0070] The present invention also relates to a biocidal polyurethane-iodine complex that is active against, for example, bacteria, viruses, yeasts, fungi, moulds, spores and / or protozoa. In particular, it provides a PU-I complex that is obtainable by the method according to the present invention. The PU-I complex can be prepared by the in situ method according to the present invention or by complexing a preformed TPU with iodine under the conditions described above. The PU-I complex is characterised by the absence or near absence of detectable release or leaching of iodine from the PU material. The PU-I complex can comprise a thermoplastic PU (herein also referred to as TPU-I) or a thermoset PU or an aqueous PUD.

[0071] In one aspect, the present application provides a polyurethane-iodine complex comprising 1-30 wt% PVP-I, such as 2-15 w% PVP-I, 3-10 w% PVP-I, or 3-8 w% PVP-I.

[0072] In another aspect, the present application provides a polyurethane-iodine complex comprising 0.1-30 wt% elemental iodine (I2), such as 0.1-20 w%, 1-15 w%, or 3-8 w% elemental iodine. In a preferred embodiment, the PU-I complex comprises 0.1-10 wt% elemental iodine. For example, provided is a polyurethane-iodine complex having soluble iodine in an amount of at least 0.1 wt% in the finished polyurethane-iodine complex material.

[0073] As will be appreciated by those skilled in the art, the PU-I complexes provided herein can be prepared or formulated in any suitable form, composition, or material. These materials include foams, dispersions, coatings, solid articles, and the like. Preferably, the PU is the predominant polymer. In one embodiment, the TPU comprises at least 85 wt%, preferably at least 90 wt%, and more preferably at least 95 wt% of the total polymer content of the PU-I containing material. Alternatively or additionally, the material is free of hydrophilic polymers, preferably free of poly(N-vinyl lactam).

[0074] The PU-I materials of the present application are functionally characterized by combining desirable mechanical properties with broad spectrum biocidal and antiviral activity against bacteria, mold, viruses, and fungi. The materials are non-toxic, non-irritating, and non-sensitizing, and have broad applications in the hygiene, consumer, food, veterinary, aquaculture, and industrial fields.

[0075] Accordingly, the present application also provides the use of the polyurethane-iodine complex according to the present application in numerous (biocidal) applications, including the fields of industrial, construction, consumer, pharmaceutical, hygiene, veterinary, and / or aquaculture markets. The use can involve the polyurethane-iodine complex forming a blend, composite, and / or interpenetrating network with other natural or synthetic polymers, natural or synthetic fibers, biocides, and / or fillers.

[0076] As can be seen from the foregoing, the present application also relates to a biocidal product (i.e., a final product or consumer product) comprising the polyurethane-iodine complex provided herein. Also herein, the polyurethane-iodine complex can be part of a blend, composite, and / or interpenetrating network with one or more other natural or synthetic polymers, natural or synthetic fibers, biocides, and / or fillers. Exemplary biocidal products include air filters, water and solution filters, masks, gloves, equipment or device housings, adhesives, clothing, window coverings, fibers, hard surface coatings, dental products, building materials, construction materials, carpets, medical devices, wound dressings, tissue scaffolds, surgical and endoscopic devices, catheters, tubes, breathing tubes, endotracheal tubes, intravascular catheters, deep intravenous lines, footwear, sponges, cutting planks, face shields, hoses, food and equipment packaging, countertops, flexible surface coatings, keyboards, upholstery, floor coatings, flooring, condoms, elastic bands, heart valves, pacemakers, mats, mattresses, sealants, breast implants, implants, foams, and gaskets.

[0077] Also provided is an aqueous dispersion comprising the biocidal PU-I complex according to the present application, and its use in a method of providing a biocidal coating to a surface or object. In another embodiment, the present application provides a biocidal coating comprising or consisting of the PU-I complex according to the present application. The present application also includes an object, such as a face mask, at least partially provided (e.g., by spraying) with the biocidal PU-I complex. DETAILED DESCRIPTION

[0078] Because complexation can be carried out on a wide range of PUs with unique and desired properties, the potential applications of the PU-I complex articles are the same as those currently used for PUs, with the added benefit of being biocidal. Furthermore, because the PU-I complex is manufactured in the melt, the resulting material has inherent biocidal properties throughout the polymer matrix. The PU-I system exhibits broad-spectrum biocidal activity against bacteria, viruses, yeasts, fungi, molds, and protozoa. The biocidal activity of the PU-I material is nonselective and can be used where PU materials with bactericidal, fungicidal, viricidal, sporocidal, amoebicidal, insecticidal, or nematocidal activity are required. The resulting PU-I complex and blend products are low in animal and plant toxicity, nonirritating to skin and mucous membranes, nonallergenic, do not delay healing or form granulation tissue, and are nonirritating. The PU-I complex of the present application exhibits long-term biocidal activity.

[0079] The PU-I complex material disclosed herein is expected to have a broad spectrum biocidal activity similar to water soluble PVP-I complex. PVP-I solutions are effective against: bacteria, bacterial spores, yeast, mold, fungi, viruses, and bacteriophages. PVP-I materials show a broader biocidal activity than other antiseptics such as benzalkonium chloride and chlorhexidine. Unlike many antibiotics, no bacterial resistance has been observed with PVP-I systems after more than 60 years of clinical use. PVP-I solutions are active against methicillin-resistant Staphylococcus aureus (MRSA), Klebsiella pneumoniae, Streptococcus pneumoniae, Haemophilus influenzae, Pseudomonas aeruginosa, and Legionella pneumophila, and readily inactivate human immunodeficiency virus (HIV) and poliovirus. PVP-I solutions show high virucidal efficacy against avian influenza (Virology J., 2009:6: 124), Ebola virus, and vaccinia virus Ankara, which is used as a reference virus to show virucidal activity against enveloped viruses (BMC Infect Dis., 2015; 15: 375). PVP-I has also been shown to be highly active against SARS coronavirus SARS-CoV (Dermatology, 2006; 212(suppl 1): 119-123), which is in the same family as the virus that caused the global outbreak of COVID-19 and the subsequent global economic crisis.

[0080] PVP-I is available as a red-brown free-flowing powder. Typically, it is available with an iodine content of about 9-12%. The material has been listed in the USP and EP Pharmacopoeias. Details of how to make the PVP-I complex are given in US Patent 4,200,710, and there are many manufacturers of PVP-I worldwide, including Ashland Inc., BASF, and Boai NKY Pharmaceuticals Ltd.

[0081] Suitable PU and / or PU raw materials for use in the present application include raw materials produced by a number of global manufacturing companies, including: BASF Europe, Bayer, Covestro, Lubrizol, DSM, Dow, BorsodChem, Elastogran, Huntsman Polyurethanes, LyondellBasell, Repsol, Emery Oleochemicals, and Shell Chemicals. These materials include polyurethane thermoplastic materials and raw materials for making polyurethane thermoset materials, primarily polyols and / or isocyanates.

[0082] According to the present application, the PU-I complex can be made by dissolving the desired iodine source into the resulting structure of the PU without the need for additional solvents. This is achieved, for example, by (1) dissolving the iodine source into the PU in the molten phase, such as a TPU; (2) dissolving the iodine source into one or more starting materials used to produce the PU, such as a polyol and / or isocyanate; or (3) adding the iodine source to an aqueous polyurethane dispersion (PUD).

[0083] Common commercially available aromatic isocyanates include toluene diisocyanate (TDI), diphenylmethane diisocyanate (MDI), naphthalene diisocyanate (NDI), triphenylmethane triisocyanate, and polymeric forms of MDI and TDI. Common commercially available aliphatic isocyanates include hexamethylene diisocyanate (HDI), isophorone diisocyanate (IPDI), and hydrogenated MDI (HMDI).

[0084] In addition to the above-mentioned commercial isocyanates, the present application can also employ a range of specialty diisocyanates and polyfunctional isocyanates. Modified polyfunctional isocyanates, which are products resulting from the partial chemical reaction of organic isocyanates and / or polyfunctional isocyanates, can be used. Examples include, but are not limited to, diisocyanates and / or polyfunctional isocyanates containing ester groups, ether groups, urea groups, biuret groups, allophanate groups, carbodiimide groups, isocyanurate groups, and / or urethane groups.

[0085] The polyol component can be any conventional polyol used to form polyurethanes. Exemplary polyols include polyhydroxyl-containing polyesters, polyoxyethylene polyether polyols, polyhydroxyl-terminated polyurethane polymers, polyhydroxyl-containing phosphorus compounds, and polyhydroxyl polythioesters, polyacetals, aliphatic polyols, and alkylene oxide adducts of mercaptans, and mixtures thereof. Commercial polyether polyols include hydroxyl-terminated polypropylene oxide (PPO), polypropylene glycol (PPG), hydroxyl-terminated polyethylene oxide, polyethylene glycol (PEG), and polytetramethylene oxide (PTMO), and polytetrahydrofuran (PTHF) polyols. Commercial polyester polyols are typically made from adipic acid and ethylene glycol (polyethylene adipate) or butylene glycol and adipic acid (polybutylene adipate). In addition, the polyester polyols can be made from mixtures of diols and adipic acid to control the mechanical properties of the resulting polyol. Another important polyol is the polycaprolactone diol, which is considered biodegradable. Polyols can also be made by copolymerization of caprolactone with other monomers. Much work has also been done in developing bio-based polyols to improve sustainability.

[0086] The PU composition can further include a chain extender. The chain extender can be an aromatic or aliphatic compound capable of reacting with at least two isocyanate-terminated polymer units to form a polymer chain. Typical chain extenders can be aromatic or aliphatic compounds having more than one hydroxyl or amine group at the end. Other PU components include: catalysts, surfactants, stabilizers, dyes, thickening agents, plasticizers, fillers, and pigments. The PU family of polymers represents one of the most extensive and diverse families of synthetic polymers. PolyPUs can also be easily blended or compositely constructed with other polymers and substrates to further expand the range of available properties and applications.

[0087] Very good results can be obtained in preparing a homogeneous mixture of (i) at least one iodine source and (ii) a thermoplastic polyurethane (TPU) or polyurethane dispersion (PUD) to form a single phase system, so that a biocidal PU-I complex can be formed. As previously mentioned, the PU-I biocidal material of the present invention can be prepared without the use of solvents. For thermoplastic polyurethane (TPU) systems, the TPU-I complex can be formed by blending the TPU polymer with a suitable iodine source in the molten state. The TPU-I complex can be easily and effectively prepared by hot melt extrusion, and the finished product can be manufactured by extrusion, injection molding, or 3-D printing. Hot melt extrusion can be used to achieve the melt mixing and preparation of the TPU-I complex and the manufacture of the finished product, and can also be used to prepare a masterbatch for further downstream processing and product production. The preferred temperature for complexation depends on the TPU base material and the iodine source, with the preferred minimum extrusion temperature being higher than the melting temperature of iodine (114°C) so that the TPU matrix and iodine are mixed quickly and efficiently. The actual TPU-I extrusion conditions are very dependent on the TPU material being blended with the iodine and PVP-I material. Acceptable TPU materials that can be blended with iodine and / or PVP-I in the hot melt are any TPU that can be melted and extruded, including but not limited to: polyester-based TPU, polyether-based TPU, caprolactone-based TPU, aromatic TPU, and aliphatic TPU. TPU is a block copolymer consisting of alternating soft and hard segments that can be controlled to form an almost infinite number of TPU's. TPU block copolymers include polar, strong hard segments formed by the reaction of diisocyanates with short chain diols (chain extenders) and polar, weak soft segments formed by the reaction of diisocyanates with long chain diols. By adjusting the ratio of soft and hard segments, a wide variety of polymer properties of TPU's with different melt characteristics and mechanical properties can be synthesized. The soft and hard segments separate into distinct phases, forming crystalline or pseudo-crystalline phases, physically cross-linking the thermoplastic polyurethane upon cooling. Heating the TPU causes these "pseudo-crosslinks" to disappear, melting the TPU. It is during this melting process that the iodine source can be effectively complexed into the TPU matrix. Upon cooling, the hard and soft segments begin to phase separate, and the TPU-I complex physically cross-links, "fixing" the biocidal TPU-I complex in the desired form and shape. Since the resulting TPU-I can be melted, the TPU-I material can be easily processed by extrusion, injection molding, blow molding, fabric coating, over molding, calendering, compression molding, vacuum forming, solution coating, and 3-D printing.

[0088] TPU commercial products are available from many manufacturers, including: Pellethane TM , Tecoflex TM , Tecothane TMCarbothane TM TPU; Huntsman Corporation TPU; Covestro AG TPU; BASF Europe TPU; Dow Chemical's DIPRANE TM HYPERLAST TPU TM Epaflex Polyurethanes Spa's EPACOL TK, EPALINE, EPAMOLD, and Pakoflex; Polyvent's Edgetek TM Gravi-Tech TM NEUSoft TM OnFlex TM Wanhua Chemical Group Co., Ltd. TPU; Coim Group's LARIPUR TPU; Taiwan's Hsin Shun TPU; Miragnn Chemical Company TPU; Miracil Chemicals TPU; and Hexpol TPE's Dryflex TPU. Various TPUs have a wide range of applications in many markets, including: automotive, construction and building, films and sheets, engineering, footwear, synthetic leather and fibers, hoses and pipes, medical, and wires and cables.

[0089] It should be noted that most thermoplastic polyurethanes do not require solvents during processing; therefore, the ability to form TPU-I complexes during TPU melting is crucial for obtaining a commercially viable and marketable class of TPUs. Although iodine may interact with substructural chemical groups (ester, ether, carbonate, etc.), it exhibits strong interactions and complexations with urethane and urea groups in TPU or the PU matrix.

[0090] Polyurethane dispersions (PUDs) are a relatively new type of polyurethane developed to reduce the environmental impact and health risks of solvent-based PU systems. PUDs are finely dispersed PU in an aqueous carrier, which greatly reduces or eliminates the use of solvents when applying PU coatings.

[0091] The backbone of PUDs has the same basic composition as solvent borne PU polymers, but contains hydrophilic groups that enable the polymer to disperse in water. The dispersed PU particles consist of a hydrophobic core surrounded by a hydrophilic shell consisting of ionic groups and / or long chain hydrophilic non-ionic groups. These emulsifying groups are usually attached to the polymer backbone, but sometimes external emulsifiers and solvents can be used to facilitate the production of PUDs. Ionic PUDs incorporate ionic species into the PU backbone. For example, the use of chain extenders containing sulfonate or carboxylate groups will result in the production of ionic PUDs. Non-ionic PUDs usually contain polyethylene oxide with longer segments as the hydrophilic modifier segment. Waterborne PUDs can be formulated as one and two component formulations to produce coatings with high durability, good substrate adhesion, high water resistance, stain resistance, and abrasion resistance, high toughness, and corrosion resistance. Waterborne coatings can be further formulated to undergo additional physical and chemical changes during the drying of the coating to produce a less water sensitive and / or crosslinked PU coating, further improving the performance of the resulting dried coating.

[0092] Thus, all PUs, whether thermoplastic or thermoset or PUD, that can incorporate iodine in a homogeneous and controlled manner, will form stable complexes with iodine. Therefore, any method that can homogeneously and controllably deliver and complex iodine in a polyurethane matrix in a simple manufacturing process will have broad commercial appeal. One very suitable situation for forming a TPU-I complex is when the TPU is in its "melt" physical form. A polymer melt occurs when a thermoplastic polymer is heated above its glass and / or crystallization temperature, at which point the polymer begins to behave as a viscoelastic fluid and can be processed. It is during the melting of the polymer that the iodine complex begins to initiate, form, and be available for further downstream processing and product manufacture. There are two primary methods to obtain a TPU polymer melt: (1) by heating the TPU above its glass and / or crystallization temperature, or (2) by dissolving the TPU in a solvent.

[0093] While the preferred method of manufacturing a TPU-I complex is by heating and mixing above the glass and / or crystallization temperature of the TPU without the use of solvents, in some specific applications, the TPU can be processed and then applied by solution coating. For such applications, a TPU-I solution can be made by adding the desired iodine source to the TPU during the dissolution step. The TPU-I solution is then processed as usual, the solvent removed, and the desired TPU-I complex obtained. Regardless of whether the TPU-I complex is made by heating and mixing or by solution dissolution, the actual formation of the TPU-I complex is combined with the normal and usual method steps required to process the base TPU, and no additional complex method steps are required to form the TPU-I complex.

[0094] While TPU elastomers have a wide range of uses, the largest PU family is the crosslinked thermoset PU systems. The types of thermoset PU systems include: flexible PU foams, rigid PU foams, coatings, adhesives, sealants, elastomers, adhesives, reaction injection molding (RIM), and aqueous polyurethane dispersions. PU foams can be further divided into: open cell, reticulated, or closed cell foams. For crosslinked thermoset PU systems, the production of PU-I complexes cannot be performed in the polymer melt, as PU thermosets do not melt at higher temperatures or dissolve in solvents. Therefore, the iodine source is added and dissolved appropriately in one or more of the raw materials used to produce the polyurethane thermoset, primarily the polyol, isocyanate, and / or chain extender raw materials. Iodine is very insoluble in water at 20°C (1 g of iodine can be dissolved in 3450 ml of water), but is much more soluble in alcohols, amines, and isocyanates. Higher concentrations of iodine can be made in the polyurethane raw materials and subsequently reacted to give the final PU thermoset. The ideal solubility in the polyurethane raw materials is such that the iodine loading in the final polyurethane matrix is at least 0.1 wt / wt%.

[0095] It has also been found that the addition of an iodine source to the polyurethane reaction greatly inhibits the polyurethane reaction. This can be compensated for by adding more catalyst to speed up the reaction to commercial acceptability.

[0096] The preferred iodine loading in the PU-I complex is 0.1 to 10 wt% in the finished product, but higher iodine levels can occur if subsequent dilution occurs during processing of the TPU-I system, for example, when using a masterbatch. The 0.1 to 10 wt% iodine can be achieved by using a combination of iodine sources, including elemental iodine, iodine salts, and PVP-I. When PVP-I is used, the preferred amount in the final (T)PU:PVP-I blend or finished product is 1 to 30 wt%, more preferably 1 to 20 wt%. Higher levels of PVP-I can be added without being outside the scope of the present invention. However, at high levels, the mechanical properties of the (T)PU:PVP-I material can be affected, and the resulting complex material can behave more like PVP-I (e.g., slippery when wet, PVP-I leaching from the PU matrix).

[0097] In certain cases, this can be desirable for the production of a slip coating, for example, (T)PU:PVP:I"adheres" to the substrate, while the bulk matrix is responsible for mechanical integrity, the (T)PU:PVP-I coating is used for lubrication properties and biocidal activity. In (T)PU:PVP-I thermoplastic or thermoset materials, the high loading of PVP-I also has the advantage of providing a fast release of non-complexed PVP-I for rapid and effective biocidal / antiviral activity, followed by sustained biocidal / antiviral activity from the complexed (T)PU:PVP-I. Thus, by adjusting the ratio of PVP-I to (T)PU, different biocidal / antiviral activity profiles can be easily derived depending on the application. Of course, it is also possible to produce a non-complexed iodine phase with an excess of iodine loading, however, free iodine is corrosive, irritating to the skin, and sublimates easily, so the commercial use of such a system is limited.

[0098] Another element described herein is the discovery that the biocidal / antiviral activity of the PU-I complex can be further adjusted depending on the groups present in the PU matrix. While iodine can complex with many different chemical groups, such as amide groups, carbamate groups, urea groups, the actual complexing ability of iodine to these different groups is different, which in turn, results in different activities of the resulting chemical group-iodine complex in terms of biocidal activity. Thus, since polyurethane reactions can be tightly controlled, the complexing of iodine to amide groups (by the addition of PVP-I or blending with nylon), carbamate groups, urea groups, ester groups, and ether groups can be tightly controlled by the raw materials used in the polymerization and / or processing to achieve the final (T)PU-I system and additional control over the desired biocidal (such as bactericidal, fungicidal, and virucidal) efficacy.

[0099] The PVP-I used in the present invention to make PU-PVP-I blends can have a wide range of available iodine content. Typically, the available iodine content is 1-25 wt%, with a total iodine content of 2-35 wt%. The production of this PVP-I system is outlined in US 2,706,701 and US 2,900,305 and related patents. The use of PVP-I with higher iodine content is not outside the scope of the present invention and can be desirable in some applications. The PVP precursor used to make the PVP-I complex can be a vinylpyrrolidone homopolymer or copolymer with a K value of 10-60. The preferred PVP-I material used to produce the PU-PVP-I blends is PVP-I as defined in the USP, EP, and JP Pharmacopeias, with an available iodine content of 9.0-12.0%, a nitrogen content of 9.5-11.5%, and a precursor vinylpyrrolidone homopolymer with a K value of about 30. This grade of PVP-I is widely accepted, has a long history of use, is readily available, and is listed on the World Health Organization's Essential Medicine List.

[0100] It should be noted that the preparation of blends, composites and / or interpenetrating networks (IPNs) of PU-I complexes with other natural and synthetic polymers, natural or synthetic fibers or fillers are not beyond the scope of the present invention. Such blends, composites and IPNs are also expected to benefit from the biocidal activity of the PU-I complexes. Within the scope of the present invention, the addition of one or more other biocides can also help to improve the biocidal performance of the resulting biocidal material. For example, the addition of one or more other biocides can further improve the biocidal rate and / or activity against specific strains of microorganisms while still having the broad spectrum biocidal activity of the PU-1 system. Suitable other biocides include: silver, copper, gold, zinc metals and salts thereof; quaternary amino compounds (e.g., benzalkonium chloride and cetylpyridinium chloride); phenol and cresol; halogenated phenols (e.g., p-chloro-m-xylenol); biguanides (e.g., chlorhexidine); anilines (e.g., triclocarban) and triclosan.

[0101] In addition, PU-I complexed with non-isocyanate polyurethanes (NIPU) systems are also within the scope of the present invention. NIPU are manufactured by one of the following four synthetic routes: (1) stepwise polymerization of a biscyclocarbonate and an amine; (2) stepwise polymerization of a linear activated dicarbonate and a diamine; (3) stepwise polymerization of a linear activated dicarbonate and a diol; (4) ring-opening polymerization of a cyclic carbonate. Since NIPU do not utilize isocyanates to form the PU, NIPU are generally considered to be more environmentally friendly and green than conventional polyol-isocyanate based PUs. As such, there is still an ongoing development to further push the commercialization of NIPU. Although NIPU do not utilize isocyanates for production, carbamate groups are still generated in the NIPU polymers. This carbamate group is able to complex with iodine in the same manner as conventional (T)PU systems, and NIPU-I complexes can be formed by either dissolving iodine in the NIPU thermoplastic melt through heat or solvent dissolution, or by dissolving iodine in the starting materials used to form the NIPU thermoset materials.

[0102] Another advantage of the PU-I materials of the present invention is that the biocidal iodine is naturally occurring, while the PU is readily hydrolyzable. Thus, the PU-I system is inherently biodegradable and / or can be chemically recycled by reprocessing PU-I waste or by controlled chain scission of the polyols, amines, and iodine through hydrolysis, glycolysis, alcoholysis, or aminolysis. Any iodine that enters the environment can be readily metabolized by many organisms (e.g., algae) or converted to naturally occurring iodine salts with little impact on the environment. Due to the ready availability of the materials, the "impact" on the environment is small, the price structure is good, and the ease of manufacture, the PU-I materials of the present invention have broad product potential and customer acceptance. For these reasons, the PU-I materials of the present invention are expected to have broad use, even in market areas that are highly cost sensitive. These products include, but are not limited to: water and air filters; foams for insulation, packaging, and cushioning, building materials; carpet underlayment; paints; adhesives and sealants; binders; cushioning products; footwear; automotive; elastomers.

[0103] The PU-I complexes outlined in the present invention have broad application in finished products, blends, composites, and IPNs. In theory, any potential use of PU today can become a potential use of PU-I. Applications that would particularly benefit from the present invention are those where a reduction in the risk of microbial contamination, a reduction in the risk of microbial growth, a reduction in the risk of transmission of microbial contamination, and / or viral inactivation is desired. For this reason, the PU-I system should have broad application in various industrial, consumer, pharmaceutical, health, veterinary, and aquaculture markets. Actual products include, but are not limited to: filters (both wet and dry; such as air filters for improved air quality and masks for protection of individuals from the transmission of pathogenic microorganisms and viruses), medical device coatings, devices or device housings, tapes, clothing, foams and cushions (bed, sofa), automotive, hard surface coatings (such as dishes, surgical tables), dental goods (such as aspirators, tubing, chain elastomers, restoratives, cavity liners, etc.), building and construction materials (such as flooring, insulation, adhesives, paints), carpet underlayment, medical devices, wound dressings, topical skin adhesives, surgical and endoscopic, catheters, tubing, breathing tubes, endotracheal tubes, intravascular catheters, deep vein catheters, footwear, sponges, paints, masks, synthetic sheets and fibers, textiles, food and device packaging, countertops, flexible surface coatings, keyboard covers, upholstery, artificial leather, tissue scaffolds, gloves, flooring, foams, adhesives, heart valves, cardiac pacemakers, breast implants, casting tapes, bone cements and adhesives, condoms, vaginal sponges, pads, cushioning, shock absorbing and sound dampening devices, and sealants.

[0104] All compositions, methods and experiments disclosed and claimed herein can be made and executed without undue experimentation in light of the present disclosure. While compositions, methods and experiments of this application have been described with respect to the preferred embodiments, it will be apparent to those skilled in the art that modifications and applications can be made by those skilled in the art without departing from the spirit, scope and concept of this application. All modifications and applications are intended to be within the spirit, scope and concept of the application as defined by the appended claims.

[0105] Other Embodiments of the Invention

[0106] Other Embodiment 1. A method of providing a biocidal polyurethane-iodine (PU-I) complex, the method comprising dissolving at least one iodine source into (i) a thermoplastic polyurethane (TPU) or (ii) a polymeric mixture comprising raw materials for making a polyurethane thermoset; and allowing the formation of a biocidal PU-I complex.

[0107] Other Embodiment 2. The method of other embodiment 1, the method comprising dissolving at least one iodine source in a melt or solution of a thermoplastic polyurethane to provide a thermoplastic polyurethane-iodine (TPU-I) complex.

[0108] Other Embodiment 3. The method of other embodiment 2, wherein the thermoplastic polyurethane comprises one or more of a polyester-based, a polyether-based, a polycaprolactone-based, a polyacrylate-based, an aromatic and / or an aliphatic thermoplastic polyurethane.

[0109] Other Embodiment 4. The method of other embodiment 1, the method comprising dissolving at least one iodine source in a polymeric mixture commonly used for making a polyurethane comprising (i) a polyol and (ii) an isocyanate and / or a small molecule chain extender, thereby providing a thermoset polyurethane-iodine complex.

[0110] Other Embodiment 5. The method of other embodiment 4, wherein the isocyanate comprises an aliphatic or aromatic diisocyanate or a polyfunctional isocyanate.

[0111] Other Embodiment 6. The method of other embodiment 4 or 5, wherein the polyol is selected from the group consisting of a polyether polyol, a polyester polyol, a polycarbonate polyol, a polycaprolactone polyol, a polyacrylate polyol, and any combination thereof.

[0112] Other Embodiment 7. The method of any of the preceding other embodiments, wherein the at least one iodine source is selected from the group consisting of elemental iodine, polyvinylpyrrolidone-iodine (PVP-I), an iodide salt, and combinations thereof.

[0113] Other Embodiment 8. The method of other embodiment 6, wherein the PVP-I contains 1-25% available iodine and 2-35% total iodine.

[0114] Other Embodiment 9. A biocidal polyurethane-iodine (PU-I) complex obtainable by the method according to any one of other embodiments 1-7.

[0115] Other Embodiment 10. The PU-I complex of other embodiment 9, comprising 0.1-10 wt% elemental iodine.

[0116] Other Embodiment 11. The polyurethane-iodine complex of other embodiment 9 or 10, comprising 1-30 wt% PVP-I.

[0117] Other Embodiment 12. Use of the polyurethane-iodine complex according to any one of other embodiments 9-11 in the field of industrial, construction, consumer, pharmaceutical, hygiene, veterinary and / or aquaculture markets.

[0118] Other Embodiment 13. A biocidal product comprising the polyurethane-iodine complex according to any one of other embodiments 9-11.

[0119] Other Embodiment 14. The biocidal product of other embodiment 13, selected from the group consisting of air filters, water and solution filters, face masks, gloves, equipment or device housings, adhesives, apparel, window coverings, fibers, hard surface coatings, dental products, building materials, construction materials, carpets, medical devices, wound dressings, tissue scaffolds, surgical and endoscopic devices, catheters, tubes, breathing tubes, endotracheal tubes, intravascular catheters, deep vein injection tubes, footwear, sponges, cutting boards, face shields, hoses, food and equipment packaging, countertops, flexible surface coatings, keyboards, decorative items, floor coatings, flooring, condoms, elastic bands, heart valves, pacemakers, floor mats, mattress pads, sealants, breast implants, implants, foams and gaskets.

[0120] Other Embodiment 15. The use according to other embodiment 12, or the product according to other embodiment 13 or 14, comprising the polyurethane-iodine complex in a blend, composite and / or interpenetrating network with other natural or synthetic polymers, natural or synthetic fibers, biocides and / or fillers. BRIEF DESCRIPTION OF DRAWINGS

[0121] Figure 1 : Exemplary method schematic for providing a biocidal PU-I coating by adding elemental iodine to an aqueous PU dispersion (PUD). (A) Iodine dissolved in a minimal amount of solvent is mixed with the PUD. (B) Iodine is added directly to the aqueous PU dispersion. (C) Iodine dissolved in an excess of solvent is added to the PUD. See Example 2 for details.

[0122] Figure 2 Inhibitory effect of exemplary thermoplastic TPU-I filaments on the growth of Staphylococcus aureus. See Example 4 for details.

[0123] Figure 3 Exemplary thermosetting PU-I samples 6, 8, and 11 demonstrate the inhibitory effect on the growth of (A) Candida albicans and (B) Streptococcus pyogenes. See Example 4 for details.

[0124] Figure 4 Biocide effect of exemplary PU-I foam attached to human face masks. (A) The control group PU foam showed negligible biocide activity on growth medium. (B) The PU-I foam showed significant biocide activity on growth medium. See Example 5 for details.

[0125] Experimental Section

[0126] Example 1 : Extrusion study of TPU:

[0127] A 400-gram extrusion study was conducted using a Thermo Prism Eurolab 16 twin-screw extruder with a 16 mm screw diameter and a 25 cm barrel length. The extruder barrel had five heating zones set to 200 °C, and the screw rotation speed was fixed at 400 rpm.

[0128] The raw material used is aliphatic polyether-based TPU (Lubrizol TecoFlex). TM EG-93A-B30), EP pharmaceutical grade PVP-I (Boai Xinkaiyuan Pharmaceutical Co., Ltd.) PVP-I and elemental iodine. The TPU was dried and ground before use. Both PVP-I and elemental iodine were used as is. The powder was dry-mixed in a mixer and then fed into an extruder. The extrudate in molten filament form was cooled and granulated. All extrusion experiments were conducted under nitrogen atmosphere. The filaments and granules were used "as is" to form flakes for subsequent bacterial growth studies.

[0129] Table 1: Summary of various extrusion experiments conducted using TPU.

[0130]

[0131]

[0132] Example 2: Production of PU-I complex coating from water-based PUD.

[0133] This embodiment describes the manufacture of three different PU-I coating systems by adding iodine as an iodine source to an aqueous polyurethane dispersion (PUD). Figure 3A schematic is provided illustrating the migration of elemental iodine from the continuous phase to the dispersed PU phase of each system to form a PU-I complex.

[0134] A) Iodine dissolved in a minimum amount of solvent.

[0135] A 5% (w / v) RUCO-COAT EC 4811 aqueous dispersion, which is a water-based 32% w / v aliphatic non-ionic PUD from Rudolf GmbH, was prepared. 60 ml of a 5% aqueous solution containing 3 g of polymer was stirred and 0.03 g of elemental iodine dissolved in 2 ml of isopropyl alcohol was added to the dispersion. The iodine rapidly migrated into the polyurethane phase of the dispersion to form a PU-I aqueous dispersion. The resulting opaque dispersion was cream in appearance and color. Since the elemental iodine is not soluble in water, the dissolved iodine concentrated in the polyurethane phase of the aqueous dispersion to produce the final PU-I dispersion. The resulting dispersion was stable and could be easily sprayed onto the desired object. The final dried PU-I complex contained approximately 99% PU-1 by weight and 1% iodine by weight.

[0136] B) Iodine added directly to the PU dispersion

[0137] Solid lustrous iodine provided by SQM Europe N.V. was added to the original (32 w / v%) RUCO-COAT EC 4811 aqueous dispersion. The actual amount of iodine added was 2% of the calculated amount of polymer in the PUD. The iodine rapidly settled to the bottom of the dispersion to form a multi-phase system. The phases were mixed and the iodine element was then sublimed under controlled conditions at 50°C for 12 hours to migrate the iodine element into the PU phase of the dispersion to form a PU-I complex. The PU-I dispersion was further diluted with water to obtain a 17% solid content PU-I aqueous dispersion. The resulting opaque dispersion was cream in appearance and color. The aqueous dispersion was stable and could be easily sprayed onto the desired object. The final dried PU-I complex was approximately 98% PU-2 by weight and 2% iodine by weight.

[0138] C) Iodine dissolved in excess solvent

[0139] The original 32% RUCO-COAT EC 4811 aqueous dispersion was diluted with an excess of isopropyl alcohol solution containing a small amount of dissolved iodine to obtain a soluble 5% PU-I water-alcohol solution. The resulting light brown solution was clear and stable. The final dried complex was approximately 98.5% PU-1 by weight and 1.5% iodine by weight.

[0140] Biocidal testing

[0141] Dispersion A and B and solution C containing PU-I complex were spray coated on FFP2 medical face masks - both inner and outer surfaces. The coating was dried at room temperature for 1 hour and then at elevated temperature of about 60 °C for another 30 minutes. The masks were then worn by volunteers for 3 hours, removed and the mask surfaces were spread on nutrient agar for 24 hours to observe the level of bacterial growth. All PU-I coatings resulted in reduced microbial growth from exhaled breath compared to the FFP2 control mask surfaces without PU-I coating (data not shown).

[0142] Example 3: In-situ formation of PU-I complex (polyurethane thermoset reaction)

[0143] The following raw materials were used to conduct the PU thermoset reaction:

[0144] • Hexamethylene diisocyanate (HMDI)

[0145] • Toluene diisocyanate (TDI)

[0146] • Polyethylene glycol 400 (PEG)

[0147] • Glycerol

[0148] • Polyvinylpyrrolidone K17 (PVP)

[0149] • 1,4-Diazabicyclo[2.2.2]octane (DABCO)

[0150] • Povidone-iodine (PVP-I)

[0151] • Elemental iodine (I2)

[0152] The polymerization reaction of the thermoset PU was conducted by the reaction of isocyanate with the polyol mixture of polyethylene glycol / glycerol, with or without the incorporation of iodine source. If iodine source was used in the reaction, the iodine was first dissolved in the polyol mixture before the polyurethane reaction was conducted. The polyurethane reaction including the iodine source required the addition of a catalyst (DABCO) to accelerate the reaction. Without the addition of the catalyst, the polyurethane reaction with the iodine source failed or required significantly higher curing temperature and longer reaction time to form the thermoset material.

[0153] The polyurethane reaction was conducted by reacting the isocyanate with the polyol source at room temperature to homogeneity, then the reaction mixture was poured into a mold and placed in an oven at 60 °C for 2 hours. The resulting PU-I thermoset material was then tested for biocidal activity. Table 2 summarizes the various compositions of the polyurethane thermoset materials tested for biocidal activity.

[0154] Table 2

[0155]

[0156] a Very fast reaction. No time to pour the reaction mixture into a mold.

[0157] b Very slow reaction. Some reaction did occur, but only after high temperature and long reaction times.

[0158] Example 4: Biocidal activity of PU-I complexes

[0159] The thermoplastic TPU-I samples of Example 1 and the thermoset PU-I samples of Example 3 were subjected to the following bacterial tests:

[0160] Staphylococcus aureus, Staphylococcus epidermidis, Streptococcus pyogenes and Candida albicans were grown overnight in Tryptic Soy Broth (TSB) at 37°C. 100 μl of the overnight culture was diluted to an optical density (OD600) of 0.1 at 600 nm and then spread on 100 mm Mueller-Hinton agar plates (MHA). Extruded filaments of TPU and PU thermosets were placed on the plates and the plates were then incubated at 37°C. Growth inhibition was checked at 24 and 48 hours of incubation.

[0161] As shown in Table 2, exemplary TPU samples TPU2 and TPU3 showed biocidal activity against S. aureus. The sample TPU3, which contained 3 wt% iodine, showed a clear zone of clearance. The TPU2 sample, which contained 0.5% iodine, showed a significantly smaller zone of clearance, while the original TPU1 sample showed no biocidal activity. Figure 2 Typical PU samples PU6, PU8 and PU11 were highly active against S. aureus, S. epidermidis, S. albus and S. pyogenes, showing clear zones of clearance against all microorganisms tested.

[0162] Clear zones of clearance against C. albicans and S. pyogenes were obtained. The thermoset PU samples containing lower levels of iodine appeared to have a surface biocidal effect, but did not show the clear zones of clearance as did the PU samples 6, 8 and 11. The PU samples containing no iodine source were not biocidal. Figure 3 Example 5: Manufacture and biocidal activity of PU-I thermoset foams

[0163] The following three PU-I foam systems were prepared and evaluated for biocidal (bactericidal and antiviral) activity.

[0164]

[0165]

[0166]

[0167] ​* MDI (methylene diphenyl diisocyanate)

[0168] The PU21 sample foam was then reticulated to form an open cell foam that can be used as a filter. Foams PU22 and PU23 were not reticulated.

[0169] Bactericidal test

[0170] A reticulated PU21 foam sample was cut into 2 mm thick slices and further cut into shapes suitable for standard face masks. The PU21 foam was secured to the inside of a face mask and worn by a human volunteer for 3 hours. The foam was then removed and laid on growth media overnight and bacterial colonies were observed. The same test was also performed using a similar reticulated PU foam that did not contain the PU-I complex. Figure 4 Representative photographs showing bacterial growth colonies for a normal PU reticulated foam and a PU21 PU-I complex foam are shown. They demonstrate the high biocidal activity of the PU-I complex foam of the present invention against exhaled microorganisms.

[0171] Antiviral test

[0172] Antiviral activity was measured by adding a known amount of SARS-CoV-2 virus stock to each foam sample (PU21 - PU23). The time required for the virus stock to contact the foam, then the virus supernatant was removed from the foam and dropped on 10,000 Vero E6 cells to quantitatively measure the reduction in virus titer. PU foam without iodine and no foam system were used as controls. Samples PU21, PU22 and PU23 showed significant virucidal activity against SARS-CoV-2 virus. These three samples reduced the virus by at least 90% in 10 minutes of contact time and by at least 99% in 12 hours of contact time compared to the control foam and no foam controls.

[0173] The following table summarizes the biocidal and antiviral properties.

[0174]

[0175] Example 6: Difference between adding PVP-I as a dispersion or as a solution.

[0176] This example provides the results of a comparative test between PU foams prepared by adding PVP-I to the PU polymerization mixture as a dry powder (e.g. similar to US 5,302,392) or as a solution in the PU reaction raw materials (in situ method according to the present invention).

[0177] Two identical PU reactions were performed in which PVP-I was added as a powder or as a solution. The details are shown in the following table.

[0178]

[0179] MDI (methylene diphenyl diisocyanate)

[0180] Sample 1 was performed according to US 5,302,392 (see Example I). The PVP-I powder was quickly dispersed in the polyester polyol, creating a homogeneous slurry of PVP-I powder in the polyol. Subsequently, the isocyanate MDI was added to initiate the polyurethane reaction. As expected, the reaction proceeded rapidly, creating a polyurethane foam with the PVP-I complexed powder entrapped in the polyurethane foam matrix. Since the PVP-I was not substantially dissolved in the polyol, the polyurethane reaction was not inhibited by the addition of the PVP-I powder. Consistent with the teaching of US 5,302,392, the resulting product consisted primarily of PVP-I particles dispersed / entrapped in the polyurethane foam matrix.

[0181] In the PVP-I solution reaction (Sample 2), the PVP-I was first dissolved in the chain extender diol, creating a PVP-I solution. This single phase solution was mixed with the polyol, creating a polyol / diol PVP-I solution. The subsequent polyurethane reaction with MDI was conducted under the same reaction conditions as Sample 1. However, this reaction was completely inhibited. Only after the addition of a large amount of catalyst was the reaction allowed to proceed, resulting in a homogeneous, single phase PU-I complexed foam.

[0182] As an additional control, a reaction was performed in which a PVP homopolymer (without iodine) was dissolved in the chain extender diol, creating a soluble PVP solution. The PVP solution was added to the polyol and the polyurethane reaction with MDI was conducted as in the previous experiments. The polyurethane reaction proceeded as normal, without inhibition, indicating that the inhibition of the polyurethane reaction was caused by the iodine species.

Claims

1. A method for providing a biocidal polyurethane-iodine (PU-I) complex comprising (i) dissolving at least one iodine source in a polyurethane polymeric mixture comprising a polyol to obtain a single phase iodine system, followed by (ii) conducting a PU polymerization reaction in the presence of the single phase iodine system, thereby generating a biocidal PU-I complex in situ.

2. The method of claim 1, wherein the at least one iodine source is selected from the group consisting of elemental iodine, polyvinylpyrrolidone-iodine (PVP-I), iodide salts, and combinations thereof.

3. The method of claim 2, wherein the at least one iodine source is elemental iodine, optionally in combination with PVP-I.

4. The method of claim 2 or 3, wherein the PVP-I contains 1-25% available iodine and 2-35% total iodine.

5. The method of claim 1, comprising dissolving at least one iodine source in a polymeric mixture comprising (i) a polyol; (ii) an isocyanate; and (iii) a chain extender, a crosslinker, a catalyst, a surfactant, a solvent, and / or an additive for the synthesis of a polyurethane, to provide a thermoplastic or thermoset polyurethane-iodine complex.

6. The method of claim 1, comprising dissolving at least one iodine source in a polyol, a polyol blend, a low molecular weight alcohol with functionality > 2, a low molecular weight amine with functionality > 2, and / or a solvent, followed by the addition of the desired isocyanate to initiate the polyurethane reaction.

7. The method of claim 5 or 6, wherein the isocyanate comprises an aliphatic di-, tri-, or polyisocyanate, an aromatic di-, tri-, or polyisocyanate, or any combination thereof.

8. The method of claim 5 or 6, wherein the polyol is selected from the group consisting of a polyether polyol, a polyester polyol, a polycarbonate polyol, a polycaprolactone polyol, a polyacrylate polyol, and any combination thereof.

9. The method of claim 5, wherein the chain extender is a low molecular weight diol or diamine, or any combination thereof.

10. The method of claim 5, wherein the crosslinker is a low molecular weight alcohol or amine with a functionality of 2 or more.

11. The method of claim 1, comprising the use of a polyurethane catalyst.

12. The method of claim 11, wherein the polyurethane catalyst is a tertiary amine, a metal compound, or any combination thereof.

13. The method of claim 1, wherein the polyurethane polymerization reaction is conducted by a multi-step, one-step bulk, or solvent polymerization, thereby forming the final PU-I complex in a prepolymer formation stage or one process step.

14. A method for providing a biocidal polyurethane-iodine (PU-I) complex comprising preparing a homogenous single phase system by admixing (i) at least one iodine source with (ii) a thermoplastic polyurethane (TPU) in a heated or molten state to form a single phase system that allows for the formation of a biocidal PU-I complex.

15. The method of claim 14, wherein the at least one iodine source is selected from the group consisting of elemental iodine, polyvinylpyrrolidone-iodine (PVP-I), iodide salts, and combinations thereof.

16. The method of claim 15, wherein the at least one source of iodine is elemental iodine or comprises elemental iodine.

17. The method of any one of claims 14-16, comprising dissolving the source of iodine in the TPU melt prior to extrusion.

18. A method of providing a biocidal polyurethane-iodine (PU-I) complex, comprising preparing a homogeneous mixture of (i) at least one source of iodine and (ii) a polyurethane dispersion (PUD) by adding elemental iodine to the PUD and allowing the elemental iodine to migrate into the PU phase of the dispersion to obtain a homogeneous single phase system in which a PU-I complex is formed.

19. The method of claim 18, wherein the elemental iodine is added to the PUD in the form of a solution dissolved in a suitable solvent that dissolves the elemental iodine and is compatible with the PU phase.

20. The method of claim 19, wherein the solvent is an alcohol.

21. The method of claim 20, wherein the solvent is isopropyl alcohol.

22. The method of claim 18, wherein the elemental iodine is added as a solid material followed by sublimation of the iodine.

23. The method of claim 14 or 18, wherein the TPU or PUD comprises one or more of a polyester-based, a polyether-based, a polycaprolactone-based, a polyacrylate-based, an aromatic and / or an aliphatic thermoplastic polyurethane.

24. The method of claim 14 or 18, wherein, The TPU or PUD comprises at least 85 wt% based on the total polymer content of the homogeneous mixture of PU and at least one source of iodine.

25. The method of claim 14 or 18, wherein, The TPU or PUD comprises at least 90 wt% based on the total polymer content of the homogeneous mixture of PU and at least one source of iodine.

26. The method of claim 14 or 18, wherein, The TPU or PUD comprises at least 95 wt% based on the total polymer content of the homogeneous mixture of PU and at least one source of iodine.

27. A biocidal product in the form of a foam or a solid comprising a polyurethane-iodine (PU-I) complex obtainable by the method of any one of claims 1-26.

28. The biocidal product of claim 27, wherein the PU-I complex comprises 0.1-10 wt% elemental iodine.

29. The product of claim 27 or 28, selected from the group consisting of air filters, water and solution filters, masks, gloves, equipment or device housings, adhesives, garments, window coverings, fibers, hard surface coatings, dental products, construction materials, building materials, carpets, wound dressings, tissue scaffolds, surgical and endoscopic devices, breathing tubes, endotracheal tubes, intravascular catheters, deep vein injection tubes, footwear, sponges, cutting boards, face masks, hoses, food and equipment packaging, countertops, flexible surface coatings, keyboards, upholstery, floor coatings, flooring, condoms, elastic bands, heart valves, pacemakers, floor mats, mattress pads, sealants, breast implants, foams and gaskets.

30. The product of claim 27 or 28, selected from medical devices.

31. The product of claim 27 or 28, selected from catheters.

32. The product of claim 27 or 28, selected from tubes.

33. The product of claim 27 or 28, selected from implants.

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